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Abstract The link between antibodies and bone mass is debated. Activated IgG, which interacts directly with Fc gamma receptors, stimulates osteoclastogenesis in vitro, and local injection in immune-activated mice leads to bone loss. Multiple myeloma patients with high serum IgG levels have induced osteoclast activation and display bone loss. In addition, bone loss has been linked to serum autoantibodies in autoimmune diseases, including anti-citrullinated protein antibodies (ACPA) in individuals with rheumatoid arthritis (RA). Whether serum IgG or autoantibodies regulate bone mass under healthy conditions is poorly studied. In elderly men, neither serum levels of polyclonal IgG nor autoantibody were associated with areal bone mineral density in the MrOS Sweden study. Repetitive systemic injections of high-dose polyclonal IgG complexes in mice did not exert any discernible impact on bone mineral density. However, repetitive local intra-articular injection of the same IgG complexes led to a localized reduction of trabecular bone density. These results indicate antibodies may only impact bone density when close to the bone, such as within the synovial joint.

IntroductionThe objectives of this study were: 1) to describe the socio-demographics and classify the chief complaints and reasons to encounter facilities of patients presenting to public healthcare facilities; 2) to explore differences in these complaints and: International Classification of Primary Care-3 (ICPC-3) groups across socio-demographic and health system levels.MethodsThis is a cross-sectional study conducted in three districts of Odisha, India. Within each district, the district hospital (DH), one Sub-district hospital (SDH) (if available), two Community health centers (CHCs), and two Primary health care centers (PHCs) were selected. Thus, a total of three DHs, three SDHs, six CHCs, and six PHCs were covered. Two tertiary healthcare facilities were also included. Patients aged 18 years and older, attending the Outpatient Departments (OPD) of sampled health facilities were chosen as study participants through systematic random sampling.ResultsA total of 3044 patients were interviewed. In general, 65% of the sample reported symptoms as their chief complaint for reason of encounter, whereas 35% reported disease and diagnosis. The most common reasons to encounter health facilities were fever, hypertension, abdominal pain, chest pain, arthritis, skin disease, cough, diabetes, and injury. Among the symptoms, the highest number of patients reported the general category (29%), followed by the digestive system (16%). In the disease category, the circulatory system has the highest proportion, followed by the musculatory system. In symptom categories, general, digestive, and musculatory systems were the key systems for the reasons of encounter in outpatient departments irrespective of different groups of the population. In terms of different tiers of health systems, the top three reasons to visit OPD were dominated by the circulatory system, respiratory system, and musculatory system.ConclusionThis is the first Indian study using the ICPC-3 classification for all three levels of health care. Irrespective of age, socio-economic variables, and tiers of healthcare, the top three groups to visit public health facilities according to the ICPC-3 classification were consistent i.e., general, digestive, and circulatory. Implementation of standard management and referral guidelines for common diseases under these groups will improve the quality and burden at public health facilities in India.

Age alters the host’s susceptibility to immune induction. Humoral immunity with circulating antibodies, particularly immunoglobulin G (IgG), plays an essential role in immune response. IgG glycosylation in the fragment crystallizable (Fc) region, including sialylation, is important in regulating the effector function by interacting with Fc gamma receptors (FcγRs). Glycosylation is fundamentally changed with age and inflammatory responses. We aimed to explore the regulation of humoral immunity by comparing responses to antigen-induced immune challenges in young and adult mice using a local antigen-induced arthritis mouse model. This study examines the differences in immune response between healthy and immune-challenged states across these groups. Our initial assessment of the arthritis model indicated that adult mice presented more severe knee swelling than their younger counterparts. In contrast, we found that neither histological assessment, bone mineral density, nor the number of osteoclasts differs. Our data revealed an age-associated but not immune challenge increase in total IgG; the only subtype affected by immune challenge was IgG1 and partially IgG3. Interestingly, the sialylation of IgG2b and IgG3 is affected by age and immune challenges but not stimulated further by immune challenges in adult mice. This suggests a shift in IgG towards a pro-inflammatory and potentially pathogenic state with age and inflammation.

Abstract Estradiol (E2) affects both reproductive and non-reproductive tissues, and the sensitivity to different doses of E2 varies between tissues. Membrane estrogen receptor α (mERα)-initiated signaling plays a tissue-specific role in mediating E2 effects, however, it is unclear if mERα signaling modulates E2 sensitivity. To determine this, we treated ovariectomized C451A females, lacking mERα signaling, and wildtype (WT) littermates with physiological (0.05 μg/mouse/day (low); 0.6 μg/mouse/day (medium)) or supraphysiological (6 μg/mouse/day (high)) doses of E2 (17β-estradiol-3-benzoate) for three weeks. Low-dose treatment increased uterus weight in WT, but not C451A mice, while non-reproductive tissues (gonadal fat, thymus, trabecular and cortical bone) were unaffected in both genotypes. Medium-dose treatment increased uterus weight and bone mass and decreased thymus and gonadal fat weights in WT mice. Uterus weight was also increased in C451A mice, but the response was significantly attenuated (− 85%) compared to WT mice, and no effects were triggered in non-reproductive tissues. High-dose treatment effects in thymus and trabecular bone were significantly blunted (− 34% and − 64%, respectively) in C451A compared to WT mice, and responses in cortical bone and gonadal fat were similar between genotypes. Interestingly, the high dose effect in uterus was enhanced (+ 26%) in C451A compared to WT mice. In conclusion, loss of mERα signaling reduces the sensitivity to physiological E2 treatment in both non-reproductive tissues and uterus. Furthermore, the E2 effect after high-dose treatment in uterus is enhanced in the absence of mERα, suggesting a protective effect of mERα signaling in this tissue against supraphysiological E2 levels.

Abstract Aging alters immunoglobulin production, affecting the humoral immune response. Toll-like receptor 2 (TLR2) recognizes Staphylococcus aureus (S. aureus) which causes bacteremia with high mortality in the elderly. To understand how TLR2 and aging affect the humoral immune response in bacteremia, four groups of mice (wild type-young, wild type-old, TLR2−/−-young, and TLR2−/−-old) were used to analyze immunoglobulin levels in healthy conditions as well as 10 days after intravenous injection with S. aureus. We found that aging increased the levels of both IgM and IgG. Increased IgG in aged mice was controlled by TLR2. In bacteremia infection, aged mice failed to mount proper IgM response in both wild-type (WT) and TLR2−/− mice, whereas IgG response was impaired in both aged and TLR2−/− mice. Aged mice displayed reduced IgG1 and IgG2a response irrespective of TLR2 expression. However, impaired IgG2b response was only found in aged WT mice and not in TLR2−/− mice. Both aging and TLR2−/− increased the levels of anti-staphylococcal IgM in bacteremia. Aging increased sialylated IgG in WT mice but not in TLR2−/− mice. IgG sialylation was not affected by the infection in neither of the mice. In summary, aging increases all immunoglobulins except IgG1. However, aged mice fail to mount a proper antibody response to S. aureus bacteremia. TLR2 plays the regulatory role in IgG but not IgM response to infection.

Objective: To recalibrate the Framingham Risk Score-cardiovascular diseases (FRS-CVD) using 10-year mortality data and baseline risk factor data for a rural cohort and assess the effect of recalibration on proportion categorised as high risk. Methods: Participants of a cardiovascular risk factor survey aged 30–64 years in 2011–12, from 9 villages of a rural block in Vellore, Tamil Nadu, were followed up for mortality till 2021, as part of an established demographic surveillance system. We calculated both lipid-based and Body Mass Index-based FRS-CVD risk scores, as well as recalibrated scores using risk factor data from the baseline survey and CVD mortality observed over 10 years. Results: Based on original lipid-based FRS-CVD scores, 8.48% (109) of 1285 males had a 10-year CVD risk ≥30%, compared to 11.60% (149) with recalibrated scores. Among 1737 females, 1.50% (26) had a 10-year CVD risk of ≥30%, using original FRS-CVD scores, and 3.22% (56) using recalibrated scores. Similarly, for BMI based FRS-CVD scores, overall, 3.63% (110/3028) had a 10-year risk of ≥30%, compared to 6.64% (201) using recalibrated scores.The median 10-year FRS-CVD original score in males was 7.57 (IQR: 3.67–15.83), and 2.53 (IQR: 1.28–5.32) in females, compared to 8.95 (IQR: 4.35–18.52) and 3.79 (IQR: 1.92–7.93) respectively, for the recalibrated FRS-CVD risk scores. Conclusion: The recalibrated Framingham models showed a greater proportion of the population at risk of CVDs compared to the original FRS scores, with males having 2–3 times greater CVD risk scores compared to females.

IntroductionThe glycosylation of immunoglobulin (Ig) G regulates IgG interaction capability with Fc gamma receptors found in all immune cells. In pathogenic conditions, estrogen can impact IgG levels and glycosylation. Following menopause, when estrogen levels decline affecting the immune system and potentially leading to a heightened susceptibility of immune activation.PurposeIn this study, we aim to determine if estrogen levels can regulate IgG glycosylation in postmenopausal healthy situations.MethodsMice were ovariectomized to simulate an estrogen-deficient postmenopausal status and then treated with 17-beta-estradiol (E2) at different doses and different administration strategies.ResultsUsing a highly sensitive liquid chromatography-tandem mass spectrometry (MS/MS) glycoproteomic method, we demonstrated that E2 treatment increased the degree of glycosylation on IgG-Fc with both galactosylation and sialylation in the position required for interaction with Fc gamma receptors. We also observed that only long-term estrogen deficiency reduces IgG levels and that estrogen status had no impact on total IgG sialylation on both Fab and Fc domains or general glycoprotein sialylation evaluated by ELISA. Furthermore, E2 status did not affect the total sialic acid content of total cells in lymphoid organs and neither B cells nor plasma cells.ConclusionThe study concluded that E2 treatment does not affect total serum glycoprotein sialylation but alters IgG glycosylation, including IgG sialylation, implying that estrogen functions as an intrinsic modulator of IgG sialylation and could thereby be one pathway by which estrogen modulates immunity.

Immunotherapy has revolutionized cancer treatment and revitalized efforts to harness the power of the immune system to combat a variety of cancer types more effectively. However, low clinical response rates and differences in outcomes due to variations in the immune landscape among patients with cancer continue to be major limitations to immunotherapy. Recent efforts to improve responses to immunotherapy have focused on targeting cellular metabolism, as the metabolic characteristics of cancer cells can directly influence the activity and metabolism of immune cells, particularly T cells. Although the metabolic pathways of various cancer cells and T cells have been extensively reviewed, the intersections among these pathways, and their potential use as targets for improving responses to immune-checkpoint blockade therapies, are not completely understood. This review focuses on the interplay between tumor metabolites and T-cell dysfunction as well as the relationship between several T-cell metabolic patterns and T-cell activity/function in tumor immunology. Understanding these relationships could offer new avenues for improving responses to immunotherapy on a metabolic basis.

Abstract Aim To estimate the prevalence, socio-demographic determinants, common disease combinations, and health impact of multimorbidity among a young rural population. Methods We conducted a cross-sectional survey among participants aged ≥30 years in rural Punjab, North India, from Jan 2019 to April 2019. Multimorbidity was defined as the coexistence of ≥two conditions using a 14-condition tool validated in India. We also calculated a multimorbidity-weighted index (MWI), which provides a weight to each disease based on its impact on physical functioning. Logistic regression was conducted to evaluate the association with sociodemographic variables, mental health (PHQ-9), physical functioning (ADL scale), and self-rated health (SRH). Results We analyzed data from 3213 adults [Mean age 51.5 (±13), 54% women]. Prevalence of single chronic condition, multimorbidity, and MWI was 28.6, 18% and − 1.9 respectively. Age, higher wealth index and ever use alcohol were significantly associated with multimorbidity. Overall, 2.8% of respondents had limited physical functioning, 2.1% had depression, and 61.5% reported low SRH. Poorer health outcomes were more prevalent among the elderly, women, less educated, and those having lower wealth index and multimorbidity, were found to be significantly associated with poor health outcomes. Conclusions The burden of multimorbidity was high in this young rural population, which portends significant adverse effects on their health and quality of life. The Indian health system should be reconfigured to address this emerging health priority holistically, by adopting a more integrated and sustainable model of care.

Abstract Background The growing burden of hypertension and diabetes is one of the major public health challenges being faced by the health system in India. Clinical Decision Support Systems (CDSS) that assist with tailoring evidence-based management approaches combined with task-shifting from more specialized to less specialized providers may together enhance the impact of a program. We sought to integrate a technology “CDSS” and a strategy “Task-shifting” within the Government of India’s (GoI) Non-Communicable Diseases (NCD) System under the Comprehensive Primary Health Care (CPHC) initiative to enhance the program’s impact to address the growing burden of hypertension and diabetes in India. Methods We developed a model of care “I-TREC” entirely calibrated for implementation within the current health system across all facility types (Primary Health Centre, Community Health Centre, and District Hospital) in a block in Shaheed Bhagat Singh (SBS) Nagar district of Punjab, India. We undertook an academic-community partnership to incorporate the combination of a CDSS with task-shifting into the GoI CPHC-NCD system, a platform that assists healthcare providers to record patient information for routine NCD care. Academic partners developed clinical algorithms, a revised clinic workflow, and provider training modules with iterative collaboration and consultation with government and technology partners to incorporate CDSS within the existing system. Discussion The CDSS-enabled GoI CPHC-NCD system provides evidence-based recommendations for hypertension and diabetes; threshold-based prompts to assure referral mechanism across health facilities; integrated patient database, and care coordination through workflow management and dashboard alerts. To enable efficient implementation, modifications were made in the patient workflow and the fulcrum of the use of technology shifted from physician to nurse. Conclusion Designed to be applicable nationwide, the I-TREC model of care is being piloted in a block in the state of Punjab, India. Learnings from I-TREC will provide a roadmap to other public health experts to integrate and adapt their interventions at the national level. Trial registration CTRI/2020/01/022723.

The incidence of rheumatoid arthritis (RA) increases at the same time as menopause when estrogen level decreases. Estrogen treatment is known to reduce the IgG pathogenicity by increasing the sialylation grade on the terminal glycan chain of the Fc domain, inhibiting the binding ability to the Fc gamma receptor. Therefore, treatment with estrogen may be beneficial in pre-RA patients who have autoantibodies and are prone to get an autoimmune disease. However, estrogen treatment is associated with negative side effects, therefore selective estrogen receptor modulators (SERMs) have been developed that have estrogenic protective effects with minimal side effects. In the present study, we investigated the impact of the SERM bazedoxifene on IgG sialylation as well as on total serum protein sialylation. C57BL6 mice were ovariectomized to simulate postmenopausal status, followed by ovalbumin immunization, and then treated with estrogen (estradiol), bazedoxifene, or vehicle. We found that estrogen treatment enhanced IgG levels and had a limited effect on IgG sialylation. Treatment with bazedoxifene increased the sialic acids in plasma cells in a similar manner to E2 but did not reach statistical significance. However, we did not detect any alteration in IgG-sialylation with bazedoxifene treatment. Neither estrogen nor bazedoxifene showed any significant alteration in serum protein sialylation but had a minor effect on mRNA expression of glycosyltransferase in the bone marrow, gonadal fat, and liver.

Abstract Background There is substantial interest in leveraging digital health technology to support hypertension management in low- and middle-income countries such as India. The potential for healthcare infrastructure and broader context to support such initiatives in India has not been examined. We evaluated existing healthcare infrastructure to support digital health interventions and examined epidemiologic, socioeconomic, and geographical contextual correlates of healthcare infrastructure in 544 districts covering 29 states and union territories across India. Methods The study was a cross-sectional analysis of India’s Fourth District Level Household and Facility Survey (DLHS-4; 2012–2014), the most up-to-date nationally representative district-level healthcare infrastructure data. Facilities were the unit of analysis, and analyses accounted for clustering within states. The main outcome was healthcare system infrastructural context to implement hypertension management programs. Domains included diagnostics (functional BP instrument), medications (anti-hypertensive medication in stock), essential clinical staff (e.g., staff nurse, medical officer, pharmacist), and IT specific infrastructure (regular power supply, internet connection, computer availability). Descriptive analysis was conducted for infrastructure indicators based on the Indian Public Health Standards, and logistic regression was conducted to estimate the association between epidemiologic and geographical context (exposures) and the composite measure of healthcare system. Results Data from 32,215 government facilities were analyzed. Among lowest-tier subcenters, 30% had some IT infrastructure, while at the highest-tier district hospitals, 92% possessed IT infrastructure. At mid-tier primary health centres and community health centres, IT infrastructure availability was 28 and 51%, respectively. For all but sub-centres, the availability of essential staff was lower than the availability of IT infrastructure. For all but district hospitals, higher levels of blood pressure, body mass index, and urban residents were correlated with more favorable infrastructure. By region, districts in Western India tended towards having the best prepared health facilities. Conclusions IT infrastructure to support digital health interventions is more frequently lacking at lower and mid-tier healthcare facilities compared with apex facilities in India. Gaps were generally larger for staffing than physical infrastructure, suggesting that beyond IT infrastructure, shortages in essential staff impose significant constraints to the adoption of digital health interventions. These data provide early benchmarks for state- and district-level planning.

Exercise has been shown to slow pancreatic tumor growth, but whether exercise interventions of differing volume or intensity yield differential effects on tumor outcomes is unknown. In this study, we compared three exercise training interventions implemented with and without chemotherapy on pancreatic tumor growth in mice.Methods: Male C57BL/6 mice (6–8 weeks old) were subcutaneously inoculated with pancreatic ductal adenocarcinoma tumor cells (PDAC 4662). Upon tumor detection, mice received gemcitabine 15 mg/kg intraperitoneally 3 days/week and were assigned to exercise: high volume continuous exercise (HVCE), low volume continuous exercise (LVCE), high intensity interval training (HIIT), or sedentary (SED). HVCE ran at 12 m/min for 45 min and LVCE for 15 min, 5 days/week. HIIT ran 1-min at 20 m/min, followed by 1-min walking at 8 m/min for 20 total intervals, 3 days/week. SED did not run. Additional sets of inoculated mice were assigned to the exercise interventions but did not receive gemcitabine. Tumor volume was measured every other day for 2 weeks; tumor-infiltrating lymphocytes were assessed by flow cytometry 3-week post-inoculation.Results: Tumor growth did not differ between groups that received gemcitabine (F(3, 34) = 1.487; p = 0.235; η2 = 0.116). In contrast, tumor growth differed between groups not provided gemcitabine (F(3,14) = 3.364; p = 0.049, η2 = 0.419), with trends for slower growth in LVCE than SED (p = 0.088) and HIIT (p = 0.084). Groups did not differ in tumor infiltrating lymphocytes.Conclusion: Contrary to our hypotheses, the exercise interventions compared here did not further reduce pancreatic tumor growth beyond that provided by gemcitabine. However, in mice not receiving gemcitabine, there was a trend for reduced tumor growth in LVCE.

Due to the digitization of information, organizations have abundant data in databases. Large-scale data are equally important and complex hence gathering, storing, understanding, and analyzing data is a problem for organizations. To extract information from this superfluous data, the need for dimensionality reduction increases. Soft set theory has been efficaciously applied and solved problems of dimensionality, which saves the cost of computation, reduces noise, and redundancy in data. Different methods and measures are developed by researchers for the reduction of dimensions, in which some are probabilistic, and some are non-probabilistic. In this paper, a non-probabilistic approach is developed by using soft set theory for dimensionality reduction. Further, an algorithm of dimensionality reduction through bipartite graphs is also described. Lastly, the proposed algorithm is applied to a case study, and a comparison of results indicates that the proposed algorithm is better than the existing algorithms.

ABSTRACT Inflammation has a significant effect on bone remodeling and can result in bone loss via increased stimulation of osteoclasts. Activated immunoglobulins, especially autoantibodies, can increase osteoclastogenesis and are associated with pathological bone loss. Whether immunoglobulins and mature B lymphocytes are important for general bone architecture has not been completely determined. Here we demonstrate, using a transgenic mouse model, that reduction of mature B cells and immunoglobulins leads to increased trabecular bone mass compared to wild‐type (WT) littermate controls. This bone effect is associated with a decrease in the number of osteoclasts and reduced bone resorption, despite decreased expression of osteoprotegerin. We also demonstrate that the reduction of mature B cells and immunoglobulins do not prevent bone loss caused by estrogen deficiency or arthritis compared to WT littermate controls. In conclusion, the reduction of mature B cells and immunoglobulins results in disturbed regulation of trabecular bone turnover in healthy conditions but is dispensable for pathological bone loss. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Uncertainties and fuzziness are basic phenomena in human thinking and in many real-world objectives. In the existing literature of information theory various divergence measures are available for studying such phenomena in accordance to their ethos. In general, some are probabilistic and some are non-probabilistic by nature. In the present communication, an attempt is made to introduce non-probabilistic divergence measures for fuzzy matrices that are exponential in nature. In the present study, we prove their validity and study their properties. The different applications of proposed non-probabilistic measure are discussed in the amphitheater of decision making and feature selection.

Thin layer chromatography (TLC) is considered as an efficient analytical technique used for the monitoring and identification of the adsorption behaviour of different amino acids through soil as a stationary phase amended with polyvinyl acetate at different concentration. The study gives complete idea about the mobility of four different uncharged amino acids namely glycine, alanine, tryptophan and glutamine in terms of retention factor by thin layer chromatography. Among four amino acids, highest mobility was found in case of glycine. The order of mobility was found to be in order of glycine > alanine > tryptophan > glutamine in which distilled water has been used as a mobile phase. It has been observed from the results that pH and electrical conductivity also influence mobility of amino acids. The influence of activation temperature and particle size of soil on the mobility of amino acids was also studied.

Abstract Background Hypertension and diabetes are among the most common and deadly chronic conditions globally. In India, most adults with these conditions remain undiagnosed, untreated, or poorly treated and uncontrolled. Innovative and scalable approaches to deliver proven-effective strategies for medical and lifestyle management of these conditions are needed. Methods The overall goal of this implementation science study is to evaluate the Integrated Tracking, Referral, Electronic decision support, and Care coordination (I-TREC) program. I-TREC leverages information technology (IT) to manage hypertension and diabetes in adults aged ≥30 years across the hierarchy of Indian public healthcare facilities. The I-TREC program combines multiple evidence-based interventions: an electronic case record form (eCRF) to consolidate and track patient information and referrals across the publicly-funded healthcare system; an electronic clinical decision support system (CDSS) to assist clinicians to provide tailored guideline-based care to patients; a revised workflow to ensure coordinated care within and across facilities; and enhanced training for physicians and nurses regarding non-communicable disease (NCD) medical content and lifestyle management. The program will be implemented and evaluated in a predominantly rural district of Punjab, India. The evaluation will employ a quasi-experimental design with mixed methods data collection. Evaluation indicators assess changes in the continuum of care for hypertension and diabetes and are grounded in the Reach, Effectiveness, Adoption Implementation, and Maintenance (RE-AIM) framework. Data will be triangulated from multiple sources, including community surveys, health facility assessments, stakeholder interviews, and patient-level data from the I-TREC program’s electronic database. Discussion I-TREC consolidates previously proven strategies for improved management of hypertension and diabetes at single-levels of the healthcare system into a scalable model for coordinated care delivery across all levels of the healthcare system hierarchy. Findings have the potential to inform best practices to ultimately deliver quality public-sector hypertension and diabetes care across India. Trial registration The study is registered with Clinical Trials Registry of India (registration number CTRI/2020/01/022723 ). The study was registered prior to the launch of the intervention on 13 January 2020. The current version of protocol is version 2 dated 6 June 2018.

Background: High dietary salt intake is an avoidable cause of hypertension and associated cardiovascular diseases (CVDs). Thus, salt reduction is recommended as one of the most cost-effective interventions for CVD prevention and for achieving the World Health Organization’s (WHO) 25% reduction in premature non-communicable disease (NCD) mortality by 2025. However, current and comprehensive information about national salt reduction policies and related actions across different regions are difficult to access and impede progress and monitoring. Objectives: As an initial step to developing an online repository of salt reduction policies and related actions, and to track nation-wise progress towards the WHO’s 25 by 25 goal, we aimed to identify and assess salt reduction policies and actions in select countries from two of the top five most populous regions of the world- the South-East Asia and Latin America. Methods: We conducted a literature review to identify national and regional salt reduction policies in the selected South-East Asian and Latin American countries, from January 1990–August 2020, available in English and Spanish. We also contacted selected WHO country offices (South-East Asian region) or relevant national authorities (Latin America) to gain access to unpublished documents. Results: In both regions, we found only a few dedicated stand-alone salt reduction policies: Bhutan, Sri-Lanka and Thailand from South East Asia and Costa Rica from Latin America. Available polices were either embedded in other national health/nutritional policy documents/overall NCD policies or were unpublished and had to be accessed via personal communication. Conclusions: Salt reduction policies are limited and often embedded with other policies which may impede their implementation and utility for tracking national and international progress towards the global salt reduction target associated with the 25 by 25 goal. Developing an online repository could help countries address this gap and assist researchers/policymakers to monitor national progress towards achieving the salt reduction target.

Introduction: Cardiovascular diseases (CVDs) are the leading cause of death in India. The CVD risk approach is a cost-effective way to identify those at high risk, especially in a low resource setting. As there is no validated prognostic model for an Indian urban population, we have re-calibrated the original Framingham model using data from two urban Indian studies. Methods: We have estimated three risk score equations using three different models. The first model was based on Framingham original model; the second and third are the recalibrated models using risk factor prevalence from CARRS (Centre for cArdiometabolic Risk Reduction in South-Asia) and ICMR (Indian Council of Medical Research) studies, and estimated survival from WHO 2012 data for India. We applied these three risk scores to the CARRS and ICMR participants and estimated the proportion of those at high-risk (>30% 10 years CVD risk) who would be eligible to receive preventive treatment such as statins. Results: In the CARRS study, the proportion of men with 10 years CVD risk > 30% (and therefore eligible for statin treatment) was 13.3%, 21%, and 13.6% using Framingham, CARRS and ICMR risk models, respectively. The corresponding proportions of women were 3.5%, 16.4%, and 11.6%. In the ICMR study the corresponding proportions of men were 16.3%, 24.2%, and 16.5% and for women, these were 5.6%, 20.5%, and 15.3%. Conclusion: Although the recalibrated model based on local population can improve the validity of CVD risk scores our study exemplifies the variation between recalibrated models using different data from the same country. Considering the growing burden of cardiovascular diseases in India, and the impact that the risk approach has on influencing cardiovascular prevention treatment, such as statins, it is essential to develop high quality and well powered local cohorts (with outcome data) to develop local prognostic models.

Divergence or relative information is a measure of information associated with two probability distributions of a discrete random variable which is based in Shannon entropy. In this paper a new divergence measure and corresponding fuzzy directed divergence measure have been proposed. Comparative study of the proposed divergence measure with some existing divergence measure has been done with the help of numerical example. Further, the application of proposed fuzzy directed divergence is illustrated in decision making problems.

Background: Cardiovascular diseases and diabetes are among the leading causes of premature adult deaths in India. Innovative approaches such as clinical decision support (CDS) software could play a major role in improving the quality of hypertension/diabetes care in primary care settings. Objective: To describe the steps and processes in the development of mWellcare, a complex intervention based on mobile health (mHealth) technology. Methods: The Medical Research Council framework was used to develop mWellcare in four steps: (1) identify gaps in usual care through literature review and health facility assessments; (2) identify the components of the intervention through discussions and consultations with experts; (3) develop intervention (clinical algorithms and mHealth system); and (4) evaluate acceptability and feasibility through pilot testing in five community health centers. Results: Lack of evidence-based, integrated, and systematic management of chronic conditions were major gaps identified. Experts in information technology, clinical fields, and public health professionals identified intervention components to address these gaps. Thereafter, clinical algorithm contextualized to primary care settings were prepared and the mWellcare intervention was developed. During the 2-month pilot, 631 patients diagnosed with hypertension and/or diabetes were registered, with a follow-up rate of 36.2%. The major barrier was resistance to follow mWellcare recommended patient workflow, and to overcome it, we emphasized onsite training and orientation program to cover all health care team member in each CHC. Conclusion: A pilot-tested mWellcare intervention is an mHealth system with important components, i.e. integrated management of chronic conditions, evidence-based CDS, longitudinal health data and automated short-messaging service to reinforce compliance to drug intake and follow-up visit, which will be used by nurses at primary health care settings in India. The effectiveness and cost-effectiveness of the intervention will be tested through a cluster randomized trial (trial registration number NCT02480062).

BACKGROUND:Scientific evidence indicates that high dietary salt intake has detrimental effects on blood pressure and associated cardiovascular disease (CVD). However, limited information is available on how to implement salt reduction in low and middle-income countries (LMICs) such as India, where the burden of hypertension and CVD is increasing rapidly. As part of a large study to create the evidence base required to develop a salt reduction strategy for India, we assessed the perspectives of various stakeholders regarding developing an India specific salt reduction strategy. METHODS:A qualitative research design was deployed to elicit various stakeholder's (government and policy-related stakeholders, industry, civil Society, consumers) perspectives on a salt reduction strategy for India, using in-depth interviews (IDIs) and focus group discussions (FGDs). We used an inductive approach for data analysis. Data were analyzed using thematic content analysis method. RESULTS:Forty-two IDIs and eight FGDs were conducted with various stakeholders of interest and relevance. Analysis indicated three major themes: 1. Barriers for salt reduction 2. Facilitators for salt reduction; 3. Strategies for salt reduction. Most of the stakeholders were in alignment with the need for a salt reduction programme in India to prevent and control hypertension and related CVD. Major barriers indicated by the stakeholders for salt reduction in India were social and cultural beliefs, a large unorganized food retail sector, and the lack of proper implementation of even existing food policies. Stakeholders from the food industry reported that there might be decreased sales due to salt reduction. Major facilitators included the fact that: salt reduction is currently a part of the National Multi-Sectoral Action Plan for the prevention and control of NCDs, salt reduction and salt iodine programme are compatible, and that few of the multinational food companies have already started working in the direction of initiating efforts for salt reduction. Based on the barriers and facilitators, few of the recommendations are to generate awareness among consumers, promote salt reduction by processed food industry, and implement consumer friendly food labelling. CONCLUSIONS:In this study of multiple key influential stakeholders in India, most of the stakeholders were in alignment with the need for a salt reduction programme in India to prevent and control hypertension and related CVD. The development and adoption of the National Multi-sectoral Action Plan to reduce premature non-communicable diseases (NCDs) in India, provides a potential platform that can be leveraged to drive, implement and monitor salt reduction efforts.

Purpose. To improve success of in vitro fertilization (IVF), assisted reproductive technology (ART) experts addressed four questions. What is optimum oocytes number leading to highest live birth rate (LBR)? Are cohort size and embryo quality correlated? Does gonadotropin type affect oocyte yield? Should “freeze-all” policy be adopted in cycles with progesterone >1.5 ng/mL on day of human chorionic gonadotropin (hCG) administration? Methods. Electronic database search included ten studies on which panel gave opinions for improving current practice in controlled ovarian stimulation for ART. Results. Strong association existed between retrieved oocytes number (RON) and LBRs. RON impacted likelihood of ovarian hyperstimulation syndrome (OHSS). Embryo euploidy decreased with age, not with cohort size. Progesterone > 1.5 ng/dL did not impair cycle outcomes in patients with high cohorts and showed disparate results on day of hCG administration. Conclusions. Ovarian stimulation should be designed to retrieve 10–15 oocytes/treatment. Accurate dosage, gonadotropin type, should be selected as per prediction markers of ovarian response. Gonadotropin-releasing hormone (GnRH) antagonist based protocols are advised to avoid OHSS. Cumulative pregnancy rate was most relevant pregnancy endpoint in ART. Cycles with serum progesterone ≥1.5 ng/dL on day of hCG administration should not adopt “freeze-all” policy. Further research is needed due to lack of data availability on progesterone threshold or index.

While data from the latter part of the twentieth century consistently showed that immigrants to high-income countries faced higher cardio-metabolic risk than their counterparts in low- and middle-income countries, urbanization and associated lifestyle changes may be changing these patterns, even for conditions considered to be advanced manifestations of cardio-metabolic disease (e.g., chronic kidney disease [CKD]).Using cross-sectional data from the Center for cArdiometabolic Risk Reduction in South Asia (CARRS, n = 5294) and Mediators of Atherosclerosis in South Asians Living in America (MASALA, n = 748) studies, we investigated whether prevalence of CKD is similar among Indians living in Indian and U.S. cities. We compared crude, age-, waist-to-height ratio-, and diabetes- adjusted CKD prevalence difference. Among participants identified to have CKD, we compared management of risk factors for its progression. Overall age-adjusted prevalence of CKD was similar in MASALA (14.0% [95% CI 11.8-16.3]) compared with CARRS (10.8% [95% CI 10.0-11.6]). Among men the prevalence difference was low (prevalence difference 1.8 [95% CI -1.6,5.3]) and remained low after adjustment for age, waist-to-height ratio, and diabetes status (-0.4 [-3.2,2.5]). Adjusted prevalence difference was higher among women (prevalence difference 8.9 [4.8,12.9]), but driven entirely by a higher prevalence of albuminuria among women in MASALA. Severity of CKD--i.e., degree of albuminuria and proportion of participants with reduced glomerular filtration fraction--was higher in CARRS for both men and women. Fewer participants with CKD in CARRS were effectively treated. 4% of CARRS versus 51% of MASALA participants with CKD had A1c < 7%; and 7% of CARRS versus 59% of MASALA participants blood pressure < 140/90 mmHg. Our analysis applies only to urban populations. Demographic--particularly educational attainment--differences among participants in the two studies are a potential source of bias.Prevalence of CKD among Indians living in Indian and U.S. cities is similar. Persons with CKD living in Indian cities face higher likelihood of experiencing end-stage renal disease since they have more severe kidney disease and little evidence of risk factor management.

BackgroundThe scientific evidence base in support of population‐wide salt reduction is strong, but current high‐quality data about salt intake levels in India are mostly absent. This project sought to estimate daily salt consumption levels in selected communities of Delhi and Haryana in north India and Andhra Pradesh in south India. Methods and ResultsIn this study, 24‐hour urine samples were collected using an age‐ and sex‐stratified sampling strategy in rural, urban, and slum areas. Salt intake estimates were made for the overall population of each region and for major subgroups by weighting the survey data for the populations of Delhi and Haryana, and Andhra Pradesh. Complete 24‐hour urine samples were available for 637 participants from Delhi and Haryana and 758 from Andhra Pradesh (65% and 68% response rates, respectively). Weighted mean population 24‐hour urine excretion of salt was 8.59 g/day (95% CI 7.68–9.51) in Delhi and Haryana and 9.46 g/day (95% CI 9.06–9.85) in Andhra Pradesh (P=0.097). Estimates inflated to account for the minimum likely nonurinary losses of sodium provided corresponding estimates of daily salt intake of 9.45 g/day (95% CI 8.45–10.46) and 10.41 g/day (95% CI 9.97–10.84), respectively. ConclusionsSalt consumption in India is high, with mean population intake well above the World Health Organization recommended maximum of 5 g/day. A national salt reduction program would likely avert much premature death and disability.

Background: The number and proportion of elderly persons is increasing, in India, as well as the world. Disability is an important indicator to measure disease burden in this group. While some chronic conditions may not be amenable to complete cure, their functional disabilities can be improved with timely and appropriate management. Objectives: The objective of the following study is to estimate the prevalence of functional disability and study its association with socio-demographic variables and self-reported chronic conditions among elderly persons in a rural area of Haryana. Materials and Methods: All persons aged 60 years and above in the randomly selected six clusters were included in this community-based cross-sectional study. Information was collected on socio-demographic variables and self-reported chronic conditions. Functional disability was defined as having disability in activities of daily living, or blindness or hearing impairment, or a combination of these. In multivariate analysis, backward stepwise logistic regression was carried out to study the association between the independent and dependent variables, after adjusting for confounding variables. Results: Among the 836 participants studied, the prevalence of functional disability was estimated to be 37.4% (95% confidence interval: 34.2, 40.7). The prevalence was less among men (35.9%) than women (38.8%). The prevalence increased with age, was more common among persons who were not currently married, had diabetes and chronic obstructive pulmonary disease. Conclusion: Functional disability is common among elderly persons in the rural area. Community-based interventions are needed to address them. Management of chronic conditions should include prevention and control of associated disability.

Consumer knowledge is understood to play a role in managing risk factors associated with cardiovascular disease and may be influenced by level of education. The association between population knowledge, behaviours and actual salt consumption was explored overall, and for more-educated compared to less-educated individuals. A cross-sectional survey was done in an age-and sex-stratified random sample of 1395 participants from urban and rural areas of North and South India. A single 24-h urine sample, participants’ physical measurements and questionnaire data were collected. The mean age of participants was 40 years, 47% were women and mean 24-h urinary salt excretion was 9.27 (8.87–9.69) g/day. Many participants reported favourable knowledge and behaviours to minimise risks related to salt. Several of these behaviours were associated with reduced salt intake—less use of salt while cooking, avoidance of snacks, namkeens, and avoidance of pickles (all p < 0.003). Mean salt intake was comparable in more-educated (9.21, 8.55–9.87 g/day) versus less-educated (9.34, 8.57–10.12 g/day) individuals (p = 0.82). There was no substantively different pattern of knowledge and behaviours between more-versus less-educated groups and no clear evidence that level of education influenced salt intake. Several consumer behaviours related to use of salt during food preparation and consumption of salty products were related to actual salt consumption and therefore appear to offer an opportunity for intervention. These would be a reasonable focus for a government-led education campaign targeting salt.

Objective: To determine quantitative phytochemical, anticancer and antidiabetic effect of seven Indian tropical fruit residues. Methods: In-vitro cytotoxic activity (IC50) was evaluated against cervical cancer cells (HeLa), breast cancer cells (MCF-7), hepatocellular carcinoma cells (HepG-2) and bone sarcoma cells (MG-63) and alpha amylase inhibition assay was used for antidiabetic activity. Results: Results of phytochemical analysis revealed that all residues contained remarkable amount of alkaloid, saponin, tannin and flavonoid. Notable cancer cell growth inhibition was observed for the extract from Carissa carandas pomace and Litchi sinensis seeds with IC50 values ranged from 56.72 to 89.24 μg/mL. Alpha amylase inhibition assay was measured at six different concentrations (5, 10, 25, 50, 100 and 200 mg/mL) by using different solvent extract. Results showed that Carissa carandas possessed best activity with IC50 value as 29.66 mg/mL followed by other residues in methanol extract. Conclusions: Study suggests that these fruit residues demonstrate promising antidiabetic and anticancer activity that substantiated its ethno medicinal use and may provide new molecules for the treatment of these diseases.

NbN films are grown on chemical vapor deposited graphene using dc magnetron sputtering. The orientation and transition temperature of the deposited films is studied as a function of substrate temperature. A superconducting transition temperature of 14 K is obtained for highly oriented (111) films grown at substrate temperature of 150 °C, which is comparable to epitaxial films grown on MgO and sapphire substrates. These films show a considerably high upper critical field of ∼33 T. In addition, we demonstrate a process for obtaining flexible, free-standing NbN films by delaminating graphene from the substrate using a simple wet etching technique. These free-standing NbN layers can be transferred to any substrate, potentially enabling a range of novel superconducting thin-film applications.